Stem cells refer to cells having not only self-replication ability but also the ability but also the ability to differentiate into at least two cells, and can be divided into totipotent stem cells, pluripotent stem cells, and multipotent stem cells.
Totipotent stem cells are cells with totipotent properties capable of developing into one perfect individual, and these properties are possessed by cells up to the 8-cell stage after the fertilization of an oocyte and a sperm. When these cells are isolated and transplanted into the uterus, they can develop into one perfect individual. Pluripotent stem cells, which are cells capable of developing into various cells and tissues derived from the ectodermal, mesodermal and endodermal layers, are derived from an inner cell mass located inside blastocysts generated 4-5 days after fertilization. These cells are called “embryonic stem cells” and can differentiate into various other tissue cells but not form new living organisms. Multipotent stem cells are stem cells capable of differentiating into only cells specific to tissues and organs containing these cells.
The multipotent stem cells were first isolated from adult bone marrow (Y. Jiang et al., Nature, 418:41, 2002), and then also found in other various adult tissues (C. M. Verfaillie, Trends Cell Biol., 12:502, 2002). In other words, although bone marrow is the most widely known source of stem cells, the multipotent stem cells were also found in the skin, blood vessels, muscles and brains (J. G. Tomas et al., Nat. Cell Biol., 3:778, 2001; M. Sampaolesi et al., Science, 301:487, 2003; Y. Jiang et al., Exp. Hematol., 30:896, 2002). However, stem cells are very rarely present in adult tissues, such as bone marrow, and such cells are difficult to culture without inducing differentiation, and thus difficult to culture in the absence of specifically screened media. Namely, it is very difficult to maintain the isolated stem cells in vitro.
Recently, adipose tissue was found to be a new source of multipotent stem cells (B. Cousin et al., BBRC., 301:1016, 2003; A. Miranville et al., Circulation, 110:349, 2004; S. Gronthos et al., J. Cell Physiol., 189:54, 2001; M. J. Seo et al., BBRC., 328:258, 2005). Namely, it was reported that a group of undifferentiated cells is included in human adipose tissue obtained by liposuction and has the ability to differentiate into fat cells, osteogenic cells, myoblasts and chondroblasts (P. A. Zuk et al., Tissue Eng., 7:211, 2001; A. M. Rodriguez et al., BBRC., 315:255, 2004). This adipose tissue has an advantage in that it can be extracted in large amounts, and thus, it receives attention as a new source of stem cells, which can overcome the existing shortcomings. Also, recent studies using animal model experiments disclose that adipose tissue-derived cells have the abilities to regenerate muscles and stimulate the differentiation of neural blood vessels. Thus, these adipose tissue-derived cells are being attention as a new source of stem cells.
The present inventors have previously cultured finely cut placenta tissue in a medium containing collagenase and bFGF, isolated placenta stem cells from the culture broth, and then allowed the isolated stem cells to differentiate into myocytes, osteogenic cells, neurocytes, adipocytes, chondrocytes and pancreatic beta cells (Korean Patent Publication No. 2007-0101756 A).
Meanwhile, urinary incontinence in women is caused by sagging of the urethra and bladder, which results from weakening of pelvic floor muscles arising from pudendal nerve injury due to frequent childbirth and aging. Currently, the number of female urinary incontinence patients in Korea is estimated to be about 4,000,000-5,000,000 and is increasing every year due to a rapid increase in the number of old age women. Thus, female urinary incontinence is becoming one of serious social problem worldwide. To treat urinary incontinence patients, injection therapy or surgical therapy for supporting the urethra and bladder are used. Currently, the surgical therapy which is an invasive method has a problem in that complications can occur, and the injection therapy has problems in that it employs expensive substances, and thus cannot be easily applied to all patients, and in that it has a success rate of only 50-60%, such that injection and surgery are required again.
Stem cell injection therapy does not need anesthesia and enables easy injection of stem cells into urethral sphincter. Thus, if the stem cell injection therapy can improve the contractility of urethral sphincter and increase leak point pressure, the stem cell therapy can be advantageously used to treat urinary incontinence. However, there is no study on the use of stem cells for treating urinary incontinence.
Accordingly, the present inventors have made many efforts to develop an agent for treating urinary incontinence containing stem cells and, as a result, found that placental decidua-derived stem cells or adipose-derived stem cells are effective for the treatment of urinary incontinence, thereby completing the present invention.